Project Summary/Abstract Potentiometric Probes Voltage-sensitive dyes can be applied to brain cells and tissue to study the electrical signals used by the brain to function. The fluorescent dye molecules light up under a microscope and convert tiny electrical signals to measurable changes in light intensity. Virtually all neurological disorders involve changes in the brain?s normal electrical activity and can be studied with voltage-sensitive dyes. The electrochromic voltage-sensitive dyes developed by the founders of Potentiometric Probes have extremely fast response times, one of several features that make them ideal for studying spiking in the brain?s neuronal networks. However, electrochromic dyes typically suffer from a lack of sensitivity making them difficult to use outside specialized labs. Potentiometric Probes looks to overcome this weakness with new dyes and new imaging techniques that can boost the sensitivity and information conveyed in voltage-imaging experiments. New in-vitro and in-house live cell test assays along with computational modeling will allow better optimization of voltage-sensitivity for recording neuronal spiking with the highest possible signal-to-noise. Fast, electrochromic dyes are compatible with ratiometric imaging, which has important applications for in-vivo recordings. If successful, availability of improved, better validated dyes would make voltage imaging accessible to a much wider body of researchers and provide them with a more powerful tool for studying the electrical signals underlying normal and pathological brain function.